Figure 5.

The PKR inhibitor 2-AP blocks TNF-α and C₂-ceramide-induced proteoglycan synthesis. Cartilage explants were cultured for 24 hours in the presence of 2-AP (1 mM) alone, TNF-α (100 ng/ml) with or without 2-AP (1 mM) or C₂-ceramide (100 μM) with or without 2-AP (1 mM). Explants were digested by papain (300 μg/ml) as described in Materials and methods and the amount of sGAG present determined as described above and expressed as micrograms glycosaminoglycan per milligram wet weight of cartilage. *Significantly different from control explants at P < 0.05; ** P < 0.01. 2-AP, 2-aminopurine; PKR, protein kinase R; sGAG, sulfated glycosaminoglycan; TNF, tumour necrosis factor.